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M Liebetrau

Publications and source records attributed to M Liebetrau.

10 recordsLinked to original sources
PubMed2002

A gelatin in situ-overlay technique localizes brain matrix metalloproteinase activity in experimental focal cerebral ischemia.

To determine the activity of matrix metalloproteinases (MMP), especially MMP-2 and MMP-9, which play an important role in ischemic stroke and intracerebral hemorrhage, we adapted a simple and rapid method for localizing gelatinase activity to a gelatin film in situ-overlay technique previously used in cancer research. Ten micrometer cryosections of rat brain from controls and animals subjected to 3 h of ischemia and 48 h of reperfusion (suture model for transient cerebral ischemia) were used. After thawing, a gelatin film with a polyester base was put on the slide, incubated for 24 h at 37 degrees C, stained with Ponceau S, and then discolored in bi-distilled water. Non-staining areas on the film corresponded to lysis zones, caused by activated MMPs. This was proven by MMP incubation at various concentrations on the plain gelatin film and pretreatment with EDTA (an MMP inhibitor), which prevents lysis zones in normal and ischemic brains. As confirmatory tests, SDS-PAGE zymography was used to define MMP activity, and also MMP-2 immunohistochemistry to detect the possibly cellular origin of MMPs. Normal rat brain exhibited a low background activity, which was visible as a light halo-like lysis zone over and around the brain. Areas in normal brain with medium MMP activity were within the white matter (corpus callosum, anterior commissure, and cerebellum). Ischemic brain exhibited high activity lysis zones within the infarcted area (detected by microtubuli associated protein-2 staining). These zones consisted of microscopically small lysis holes with a diameter of about 10-20 microm. Immunohistochemistry showed that especially microvessels expressed MMP antigen. SDS-PAGE zymography differentiated between a high level of activated MMPs in the ischemic area and a low level in the non-ischemic basal ganglia. The gelatin film in situ-overlay technique is able to localize MMP activity in ischemic rat brain tissue on a microscopic level.

Animals↗
PubMed2000

Plasminogen activation in experimental permanent focal cerebral ischemia.

BACKGROUND: Previous experimental work using in situ zymography has shown very early increased plasminogen activation in ischemic regions after 3 h of ischemia with and without reperfusion. The objective of the present study was to evaluate the time course and extent of plasminogen activation in long-term permanent focal cerebral ischemia. MATERIAL AND METHODS: The middle cerebral artery in male Fisher rats was irreversibly occluded by electrocoagulation. Duration of ischemia was 48, 72, and 168 h. Occlusion was controlled in vivo by MRI at day 2. Plasminogen activation was detected by in situ zymography of 10 microm cryosections with an overlay containing plasminogen and the plasmin substrate caseine. Areas of plasminogen activation were compared to structural lesions (immunohistochemical loss of microtubule-associated protein 2; MAP 2). RESULTS: Compared to controls, increased plasminogen activation was observed in the basal ganglia and the cortex of the ischemic hemisphere after 48, 72, and 168 h (affected area of basal ganglia: 44.5+/-21.9, 70.1+/-2.3 and 66.6+/-2.8%, respectively; affected area of cortex: 63.4+/-9.8, 67.7+/-0.7 and 64.0+/-3.7%, respectively). The duration of ischemia had no significant influence on the extent of plasminogen activation. Areas of increased plasminogen activation significantly overlapped with and exceeded areas of MAP 2 loss (P<0.005). DISCUSSION: Permanent focal cerebral ischemia leads to increased plasminogen activation in ischemic regions. This plasminogen activation remains elevated at persistent levels over days. It may contribute to extracellular matrix (ECM) disruption, secondary hemorrhage, and brain edema in subacute stages of ischemic stroke.

Animals↗
PubMed2000

[Gliomatosis cerebri: two case reports with atypical clinical and neuroradiologic findings].

The diagnosis of the rare disease Gliomatosis cerebri requires the correlation of clinical, radiological, and pathological findings. We report on two patients with intravitally diagnosed gliomatosis cerebri. Due to the unusually high malignancy of the tumor cells, diagnosis was complicated by atypical findings such as gadolinium enhancement in MRI and raised intracranial pressure. The clinical course, differential diagnosis, and literature are summarized briefly.

Biopsy↗
PubMed2000

Plasminogen activation in focal cerebral ischemia and reperfusion.

In focal cerebral ischemia the plasminogen-plasmin system plays a role in the fibrinolysis of vessel-occluding clots and also in the proteolysis of extracellular matrix components, which potentially contributes to brain edema and bleeding complications. The authors investigated the plasminogen activation after middle cerebral artery occlusion with and without reperfusion (reperfusion intervals 9 and 24 hours) in rats by histologic zymography and compared areas of increased plasminogen activation to areas of structural injury, which were detected immunohistochemically. After 3 hours of ischemia, increased plasminogen activation was observed in the ischemic hemisphere. The affected area measured 5.2%+/-8.5% and 19.4%+/-30.1% of the total basal ganglia and cortex area, respectively. Reperfusion for 9 hours after 3 hours of ischemia led to a significant expansion of plasminogen activation in the basal ganglia (68.8%+/-42.2%, P < 0.05) but not in the cortex (43.0%+/-34.6%, P = 0.394). In the basal ganglia, areas of increased plasminogen activation were related to areas of structural injury (r = 0.873, P < 0.001). No such correlation was found in the cortex (r = 0.299, P = 0.228). In this study, increased plasminogen activation was demonstrated early in focal cerebral ischemia. This activation may promote early secondary edema formation and also secondary hemorrhage after ischemic stroke.

Animals↗
PubMed1999

Increased intracellular calpain detection in experimental focal cerebral ischemia.

Calpains are intracellular proteinases whose proteolytic activity is directed mainly against the cytoskeleton and regulatory proteins. We studied the presence of calpain by immunohistochemistry in a rat model of reversible focal cerebral ischemia (3 h) at various times of reperfusion. The numbers of calpain-positive cells on the ischemic side were compared with the non-ischemic side. In controls only 2 +/- 1% cells were positive, whereas the cortex of the ischemic vs the non-ischemic side showed 88 +/- 3% vs 13 +/- 4% calpain-positive cells (p < 0.001), and the basal ganglia 47 +/- 3% vs 13 +/- 4% (p < 0.01) after 3 h ischemia and 24 h reperfusion. This is the first demonstration of elevated intracellular levels of calpains in areas of cerebral ischemia. Longer reperfusion resulted in an increase in calpain positivity.

Animals↗
PubMed1999

[Nocturnal gastroesophageal reflux as a cause of refractory chronic laryngitis--pathophysiology and management].

Chronic laryngitis is a common disease with a multifactoral genesis. One of the known causal factors is gastrolaryngeal acid reflux as a consequence of gastroesophageal reflux disease (GERD). 10 to 30% of the patients do not show an adequate response to the standard treatment with proton pump inhibitors, which could not be well explained in the past. Our own observations indicate, that sleep related gastroesophageal reflux may play an important role. The special physiological conditions in sleep can impair the reflux, and an increased nocturnal breathing effort in snoring or sleep apnea induces an intensive gastrolaryngeal reflux. This paper explains the pathophysiological background and the diagnostics and differential treatment.

Adult↗
PubMed1994

Novel path to apoptosis: small transmembrane pores created by staphylococcal alpha-toxin in T lymphocytes evoke internucleosomal DNA degradation.

Peripheral-blood human T lymphocytes were treated with Staphylococcus aureus alpha-toxin. Membrane permeabilization was assessed by measuring efflux of K+ and Rb+ and influx of Na+, Ca2+, and propidium iodide. Cellular ATP and [3H]thymidine incorporation following lectin stimulation were measured as parameters for cell viability. Internucleosomal cleavage characteristic of programmed cell death was assessed by agarose gel electrophoresis and by quantifying low-molecular-weight, [3H]thymidine-labeled DNA fragments. Nanomolar concentrations of alpha-toxin evoked protracted, irreversible ATP depletion in both activated and resting T lymphocytes. Toxin-damaged cells also lost their ability to incorporate [3H]thymidine upon subsequent stimulation with phytohemagglutinin. These cells carried toxin hexamers, and their plasma membranes became permeable for monovalent ions but not for Ca2+ and propidium iodide. The permeabilization event was followed by internucleosomal DNA degradation characteristic of programmed cell death. Membranes of cells treated with high toxin doses (> 300 nM) became permeable to both Ca2+ and propidium iodide. In this case, ATP depletion occurred within minutes and no DNA degradation was observed. When cells were suspended in Na(+)-free buffer, alpha-toxin applied at low doses still bound and formed hexamers. However, these cells displayed neither DNA degradation nor loss of viability. The data indicate that formation of very small but not of large alpha-toxin pores may trigger programmed cell death in lymphocytes and that uncontrolled flux of Na+ ions may be an important event precipitating the suicide cascade.

Adenosine Triphosphate↗
PubMed1993

[Reproducible ventricular flutter during programming of a DDD pacemaker].

A bipolar DDD pacemaker system was implanted in a 51-year-old woman with a 2 degrees (Mobitz type) atrioventricular block. The first postimplantation control was unremarkable, but she collapsed 9 weeks later with dyspnoea, tachycardia and profound perspiration. Ventricular flutter occurred twice during routine ambulatory pacemaker function tests one week later. The first episode was terminated by a precordial blow with a fist, but the second required electrical defibrillation. During the subsequent hospitalization abnormal electrolyte balance and digitalis intoxication were excluded. Left-heart catheterization with coronary angiography showed normal left-ventricular function at rest and normal coronary arteries. There was no evidence for an arrhythmogenic right ventricle. Electrophysiological testing with programmed ventricular stimulation provoked ventricular tachycardia with torsade de pointes and transition to ventricular fibrillation. Antiarrhythmic treatment with sotalol, 160 mg twice daily by mouth, failed to suppress the episodes of torsade de pointes. But further programmed ventricular stimulation was uneventful after the sotalol dosage had been increased to 160 mg three times daily.

Female↗
PubMed1993

[Congenital fistulas of the coronary arteries. A review with case presentations].

Coronary artery fistulas are rare atypical communications between a coronary artery and a cardiac chamber or other great vascular structure and usually congenital in origin. Many are detected accidentally by the use of coronary angiography. These fistulas often have minor hemodynamical significance and the course is primarily from the proximal left coronary artery to the pulmonary artery. Though symptoms are rare they should be observed carefully in aspect of possible complications. In contrast sometimes coronary artery fistulas are found when searching for the cause of cardiac murmurs or clinical symptoms. Great amounts of shunted blood can result in cardiac volume overload and myocardial ischemia may occur by coronary steal. Surgical closure of these fistulas is the treatment of choice. In our laboratory we found in a series of 3,000 coronary angiographies a 53 year old man with an abnormal communication from the right coronary artery to the right atrium and a 68 year old woman with a fistula from the proximal left anterior descending artery to the pulmonary artery.

Aged↗